From malaria control to sustainable elimination: Cluster randomised trial comparing targeted versus generalised vector control in South Africa

已将疟疾发病率降至较低水平的国家在试图完全消灭这种疾病时面临重大挑战。为了进一步减少传播，需要大量资源用于通过控制蚊虫媒介来预防疾病，例如在所有房屋进行室内残留喷洒。这种大规模预防工作可能导致不再认为存在疟疾风险的社区和控制项目的依从性降低，并在疾病负担较低时削弱政治和捐助者的承诺，从而危及消除工作的可持续性。必须开发以证据为基础的缩减一揽子IRS的方法，以确保当IRS不再常规应用时，人群不会处于危险之中。在本研究中，针对新报告病例的有针对性的重点IRS将与所有房屋的一般年度IRS进行比较，以确定它是否同样有效、成本更低、更可接受、导致更高的覆盖率和依从性，并增加寻求疟疾预防的行为。这一方法的先决条件是建立一个可靠的快速疟疾病例监测系统，该系统以对疑似病例的明确诊断为基础。这项试验将在南非进行，南非实行了几十年的地毯式IRS，许多地区的病例发病率现在低到足以被认为是预先消除，并且建立了高质量的病例报告系统。喷洒地点将分成5000至10000人的集群，随机分配到目标IRS或一揽子常规IRS。针对在4周内发生且彼此相距0.5公里范围内的两个或更多当地病例，将触发有针对性的社区IRS。将在每个病例屋0.5公里半径范围内开展喷洒和社区宣传活动。假定局部喷洒将导致更高质量的IRS应用，因为它可以得到更好的监督，并将被视为防止因最近发生的局部病例而造成的真正感染风险的保护；它将更容易被住户接受，从而导致更好的合作，进入房屋，从而提高喷雾覆盖率；而且户主将更好地遵守在喷洒后不重新粉刷、清洗或重新抹灰的规定。因此，我们预计，在IRS的目标地区，病例发生率不会高于接受大规模IRS的地区，并且有针对性的喷洒将更经济，因此更具可持续性。这项研究将衡量疟疾病例发生率、住户接受程度和依从性、喷雾覆盖率以及干预措施的经济成本，作为结果指标。来自其他国家的一些证据表明，在传播率极低的环境中，偶发疟疾病例发生在长期稳定的热点地区。如果能够准确定位这些热点，就可以挑选出它们进行重点干预，例如在每个季节开始时进行有针对性的IRS。为了调查南非是否存在这样的局部传播热点，建议在开展靶向IRS的社区收集滤纸血点，检测是否存在疟疾抗原抗体血清阳性。将把“暴发”社区的血清患病率与随机选择的近期未发生病例的社区的血清患病率进行比较。这种比较将确定最近发生病例的社区在历史上是否暴露于疟疾寄生虫，从而可能成为传播热点。这些热点的存在将加强有针对性的控制努力。对于将消灭疟疾作为政策目标的国家来说，这项研究将提供证据，在消灭前阶段可根据这些证据作出关于大规模病媒控制的可持续政策决定。

Countries that have reduced malaria incidence to low levels face major challenges when trying to eliminate the disease altogether. In trying to reduce transmission further, considerable resources are required for disease prevention through mosquito vector control, for example by indoor residual spraying (IRS) of all houses. Such mass prevention efforts can lead to reduced compliance in communities and control programs who no longer perceive a risk of malaria, and waning political and donor commitment when the disease burden is low, thereby endangering the sustainability of the elimination effort. Evidence based methods of scaling back blanket IRS have to be developed which ensure that populations are not put at risk when IRS is no longer routinely applied.In this study, targeted focal IRS in response to new cases being reported will be compared with generalised annual IRS of all houses, to determine whether it is as effective, less costly, more acceptable, results in higher coverage and compliance and increased malaria prevention seeking behaviour. A pre-condition for this approach, is a reliable rapid malaria case surveillance system, based on definitive diagnosis of suspected cases. This trial will be carried out in South Africa, which has practised blanket IRS for many decades, where case incidence in many districts is now low enough to be considered pre-elimination, and where a high quality case reporting system is well established. Spray localities will be grouped into clusters of 5,000 to 10,000 persons which will be randomly allocated to either targeted IRS, or to blanket routine IRS. Targeted neighbourhood IRS will be triggered in response to two or more local cases occurring within 4 weeks of each other and residing within 0.5km from one another. Spraying and community awareness activities will be carried out in a radius of 0.5km from each case house. It is postulated that focal spraying will lead to higher quality of IRS application because it can be better supervised and will be seen as protection against real risk of infection due to the occurrence of recent local cases; that it will be more acceptable to householders and hence lead to better co-operation with access to premises and hence higher spray coverage; and that householders will exercise better compliance with not repainting, washing or re-plastering of walls after spraying. As a result we expect that incidence of cases will be no higher in targeted IRS areas than in those receiving mass IRS and that targeted spraying will be more economical and hence more sustainable. The study will measure malaria case incidence, householder acceptability and compliance, spray coverage, and economic costs of the interventions as outcome indicators.There is some evidence from other countries that in very low transmission settings, incident malaria cases occur in hotspots that are stable over time. If such hotspots can be accurately located, they can be singled out for focal interventions such as targeted IRS at the beginning of each season. To investigate whether such hotspots of local transmission exist in South Africa, it is proposed that filter paper blood spots are collected in communities where targeted IRS is carried out, to be tested for the presence of antibody sero-positivity to malarial antigens. The sero-prevalence of 'outbreak' communities will be compared with sero-prevalence of randomly selected communities in which no recent cases have occurred. This comparison will determine whether neighbourhoods with recent cases have historically been exposed to malaria parasites, and are therefore likely to be hotspots of transmission. The existence of such hotspots would strengthen the case for targeted control efforts.For countries that have set elimination of malaria as a policy objective this study will provide evidence upon which sustainable policy decisions about mass vector control can be based during the pre-elimination period.